The use of toxins as tools in neurophysiological studies began with the discovery of Tetrodotoxin. Thereafter the application of neurotoxins isolated from scorpion venoms has been widely investigated.
More than 110 different polypeptides have been isolated and characterized from the venom of 21 different species of scorpions which exist in different geographical regions of the world.
The chemical structure of many toxins from scorpion venom has been studied and has been found to consist of compact molecules, stabilized 3 to 4 disulphide bridges with two-and-half turns of alpha-helix and three-strand stretch of antiparallel beta sheet which runs parallel to the alpha-helix. These data were obtained by X-ray diffraction and circular dichroism studies. The use of optical rotatory dispersion measurements has shown that some toxins from the venom of Centruroides noxius and Tityus serrulatus are highly thermostable: they can be boiled for five minutes and still fold back to their original three-dimensional structure, preserving their toxicity. Two families of toxins have been isolated: one with a short chain (approximately 39 amino acid residues) and another with a long chain (61 to 70 amino acid residues).
In order to obtain information on the active site of these peptides, several chemical modifications have been carried out on some known toxins and it has been found that a reduction of the disulphide bridges, a modification of the carboxylic groups and acetylation of amino groups can change their toxicity. This suggests the importance of some amino acids in the toxin's activity.
The applicant has carried out comparative studies into the primary structure of scorpion toxins using the method of metric analysis with which it has established the existence of at least five different groups of toxins with similary homologous amino acid sequences in which the preservation of cysteines in all the toxins studied seems to be very important for the stabilization of the molecules, and hence for their function.
Similarly, the applicant has synthesized polypeptides whose structure is related to the functioning of neurotoxins and which are the basis for the preparation of synthetic vaccines and drugs.
This invention is based on synthetically obtaining polypeptides of the Noxiustoxin type from the scorpion Centruroides noxius. This toxin represents only 1% of the scorpion's soluble venom and its effective lethal dose is in the order of 100 g. per 20 gr. of body weight of albino mice. These compounds belong to the short chain peptide family (39 amino acid residues) which are stabilized by three disulphide bridges and block potassium channels from excitable membranes.